NCT05221840

Brief Summary

This is a Phase III, randomised, double-blind, multicentre, international study assessing the efficacy and safety of durvalumab (MEDI4736) in combination with oleclumab (MEDI9447) or durvalumab (MEDI4736) with monalizumab (IPH2201) in adults with locally advanced (Stage III), unresectable NSCLC, who have not progressed following platinum-based cCRT.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Strong global presence with extensive site network
Enrollment
1,051

participants targeted

Target at P75+ for phase_3 nonsmall-cell-lung-cancer

Timeline
50mo left

Started Feb 2022

Longer than P75 for phase_3 nonsmall-cell-lung-cancer

Geographic Reach
20 countries

202 active sites

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress51%
Feb 2022Jul 2030

First Submitted

Initial submission to the registry

January 14, 2022

Completed
20 days until next milestone

First Posted

Study publicly available on registry

February 3, 2022

Completed
4 days until next milestone

Study Start

First participant enrolled

February 7, 2022

Completed
4.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 30, 2026

Expected
4 years until next milestone

Study Completion

Last participant's last visit for all outcomes

July 2, 2030

Last Updated

January 27, 2026

Status Verified

January 1, 2026

Enrollment Period

4.4 years

First QC Date

January 14, 2022

Last Update Submit

January 26, 2026

Conditions

Keywords

Non-Small Cell Lung CancerLocally Advanced NSCLC

Outcome Measures

Primary Outcomes (1)

  • Progression Free Surival (PFS)

    Progression Free Survival (PFS) as assessed by BICR, per RECIST 1.1.

    Up to 5 years after first patient randomized.

Secondary Outcomes (15)

  • Overall Survival (OS)

    Up to 9 years after first patient randomized

  • Objective response rate (ORR)

    Up to 5 years after first patient randomized

  • Overall survival (OS) at 24 months

    Up to 9 years after first patient randomized

  • Duration of response (DoR)

    Up to 5 years after first patient randomized

  • Progression free survival (PFS) at 6, 12, 18, and 24 months

    From date of randomization until 24 months

  • +10 more secondary outcomes

Study Arms (3)

Arm A: Durvalumab and Oleclumab

EXPERIMENTAL

Durvalumab on Day 1 of each 28-day cycle + Oleclumab on Days 1 and 15 of cycles 1 and 2, then on Day 1 of each subsequent 28-day cycle for up to 12 months

Drug: DurvalumabDrug: Oleclumab

Arm B: Durvalumab and Monalizumab

EXPERIMENTAL

Durvalumab + Monalizumab on Day 1 of each 28-day cycle for up to 12 months. Placebo infusion will be administered on Day 15 of cycles 1 and 2 only

Drug: DurvalumabDrug: MonalizumabOther: Placebo

Arm C: Durvalumab and Placebo

ACTIVE COMPARATOR

Durvalumab on Day 1 of each 28-day cycle + Placebo on Days 1 and 15 of cycles 1 and 2, then on Day 1 of each subsequent 28-day cycle for up to 12 months

Drug: DurvalumabOther: Placebo

Interventions

Durvalumab IV (intravenous infusion)

Arm A: Durvalumab and OleclumabArm B: Durvalumab and MonalizumabArm C: Durvalumab and Placebo

Oleclumab IV (intravenous infusion)

Arm A: Durvalumab and Oleclumab

Monalizumab IV (intravenous infusion)

Arm B: Durvalumab and Monalizumab
PlaceboOTHER

Placebo IV (intravenous infusion)

Arm B: Durvalumab and MonalizumabArm C: Durvalumab and Placebo

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Participant must be ≥ 18 years at the time of screening.
  • Histologically- or cytologically-documented NSCLC and have been treated with concurrent CRT for locally advanced, unresectable (Stage III) disease
  • Provision of a tumour tissue sample obtained prior to CRT
  • Documented tumour PD-L1 status by central lab
  • Documented EGFR and ALK wild-type status (local or central).
  • Patients must not have progressed following definitive, platinum based, concurrent chemoradiotherapy
  • Participants must have received at least 2 cycles of platinum-based chemotherapy concurrent with radiation therapy
  • Participants must have received a total dose of radiation of 60 Gy ±10% (54 Gy to 66 Gy) as part of the chemoradiation therapy, to be randomised. Radiation therapy should be administered by intensity modulated RT (preferred) or 3D-conforming technique.
  • WHO performance status of 0 or 1 at randomization
  • Adequate organ and marrow function

You may not qualify if:

  • History of another primary malignancy except for malignancy treated with curative intent with no known active disease ≥5 years before the first dose of study intervention and of low potential risk for recurrence, adequately resected non-melanoma skin cancer and curatively treated in situ disease, or adequately treated carcinoma in situ or Ta tumours without evidence of disease.
  • Mixed small cell and non-small cell lung cancer histology.
  • Participants who receive sequential (not inclusive of induction) chemoradiation therapy for locally advanced (Stage III) unresectable NSCLC.
  • Participants with locally advanced (Stage III) unresectable NSCLC who have progressed during platinum-based cCRT.
  • Any unresolved toxicity CTCAE \>Grade 2 from the prior chemoradiation therapy (excluding alopecia).
  • Participants with ≥grade 2 pneumonitis from prior chemoradiation therapy.
  • History of idiopathic pulmonary fibrosis, drug-induced pneumonitis, or idiopathic pneumonitis - regardless of time of onset prior to randomisation. Evidence of active non-CRT induced pneumonitis (≥ Grade 2), active pneumonia, active ILD, active or recently treated pleural effusion, or current pulmonary fibrosis - diagnosed in the past 6 months prior to randomization.
  • Active or prior documented autoimmune or inflammatory disorders (with exceptions)
  • Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (202)

Research Site

San Diego, California, 92123, United States

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New Haven, Connecticut, 06510, United States

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Stuart, Florida, 34994, United States

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Urbana, Illinois, 61801, United States

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New Albany, Indiana, 47150, United States

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Lexington, Kentucky, 40503, United States

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Louisville, Kentucky, 40241, United States

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Annapolis, Maryland, 21401, United States

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Baltimore, Maryland, 21201, United States

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Baltimore, Maryland, 21229, United States

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Bethesda, Maryland, 20817, United States

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Grand Rapids, Michigan, 49503, United States

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Duluth, Minnesota, 55805, United States

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Billings, Montana, 59101, United States

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Ridgewood, New Jersey, 07450, United States

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Ithaca, New York, 14850, United States

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Greensboro, North Carolina, 27403, United States

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Cleveland, Ohio, 44124, United States

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Cleveland, Ohio, 44195, United States

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Maumee, Ohio, 43537, United States

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Portland, Oregon, 97239, United States

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Philadelphia, Pennsylvania, 19104, United States

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York, Pennsylvania, 17403, United States

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Sioux Falls, South Dakota, 57105, United States

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Houston, Texas, 77030, United States

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Charlottesville, Virginia, 22908, United States

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Fairfax, Virginia, 22031, United States

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Fredericksburg, Virginia, 22408, United States

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Richmond, Virginia, 23235, United States

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Richland, Washington, 99352, United States

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Spokane, Washington, 99204, United States

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Tacoma, Washington, 98405, United States

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Milwaukee, Wisconsin, 53226, United States

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Box Hill, 3128, Australia

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East Melbourne, 3002, Australia

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Elizabeth Vale, 5112, Australia

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Gosford, 2250, Australia

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Heidelberg, 3084, Australia

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Kogarah, 2217, Australia

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South Brisbane, 4101, Australia

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St Albans, 3021, Australia

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Westmead, 2145, Australia

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Barretos, 14784-400, Brazil

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Belo Horizonte, 30380-090, Brazil

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Florianópolis, 88034-000, Brazil

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Fortaleza, 60336-232, Brazil

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Jaú, 17210-120, Brazil

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Natal, 59075-740, Brazil

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Porto Alegre, 90610-001, Brazil

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Porto Alegre, 91350-200, Brazil

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Recife, 52010-075, Brazil

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São Paulo, 01323-903, Brazil

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Uberlândia, 38408-150, Brazil

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Vitória, 29043-260, Brazil

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Edmonton, Alberta, T6G 1Z2, Canada

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Barrie, Ontario, L4M 6M2, Canada

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Hamilton, Ontario, L8V 5C2, Canada

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Kingston, Ontario, K7L 2V7, Canada

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London, Ontario, N6A 5W9, Canada

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Mississauga, Ontario, L5M 2N1, Canada

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Toronto, Ontario, M5G 2M9, Canada

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Rimouski, Quebec, G5L 5T1, Canada

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Anyang, 455000, China

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Beijing, 100021, China

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Changchun, 130021, China

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Changsha, 410008, China

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Changsha, 410013, China

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Guangzhou, 510060, China

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Guangzhou, 510062, China

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Guangzhou, 510700, China

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Hangzhou, 310002, China

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Hangzhou, 310022, China

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Hefei, 133500, China

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Hefei, 230031, China

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Kunming, 650118, China

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Linhai, 317000, China

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Nanchang, 330006, China

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Nanning, 530021, China

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Nantong, 226361, China

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Neijiang, 641000, China

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Ningbo, 315100, China

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Shaoguan, 512027, China

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Tianjin, 300060, China

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Wuhan, 430022, China

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Wuhan, 430071, China

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Wuhan, 430079, China

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Zhanjiang, 524001, China

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Zhengzhou, 450000, China

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Zhengzhou, 450008, China

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Zhongshan, 528403, China

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Barranquilla, 080020, Colombia

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Bogota D.C., 110131, Colombia

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Medellín, 050034, Colombia

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Valledupar, 200001, Colombia

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Avignon, 84918, France

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Besançon, 25030, France

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Bordeaux, 33075, France

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Clermont-Ferrand, 63000, France

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Créteil, 94010, France

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Lorient, 56322, France

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Marseille, 13015, France

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Montpellier, 34298, France

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Rennes, 35033, France

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Rouen, 76031, France

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Toulouse, 31059, France

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Villejuif, 94805, France

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Erfurt, 99089, Germany

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Erlangen, 91054, Germany

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Essen, 45147, Germany

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Esslingen am Neckar, 73730, Germany

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Georgsmarienhütte, 49124, Germany

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Gütersloh, 33332, Germany

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Hanover, 30459, Germany

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Oldenburg, 26121, Germany

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Würzburg, 97080, Germany

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Brescia, 25123, Italy

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Florence, 50134, Italy

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Lucca, 55100, Italy

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Meldola, 47014, Italy

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Orbassano, 10043, Italy

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Parma, 43126, Italy

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Pavia, 27100, Italy

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Roma, 00128, Italy

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Himeji-shi, 670-8520, Japan

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Hiroshima, 730-0011, Japan

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Kashiwa, 227-8577, Japan

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Kurume-shi, 830-0011, Japan

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Natori-shi, 981-1293, Japan

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Niigata, 951-8566, Japan

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Osaka, 541-8567, Japan

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Sendai, 980-0873, Japan

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Tokushima, 770-8503, Japan

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Toon-shi, 791-0295, Japan

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Wakayama, 641-8510, Japan

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Lima, 15038, Peru

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Lima, Lima 32, Peru

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Lima, Lima 34, Peru

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Bydgoszcz, 85-796, Poland

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Gdansk, 80-952, Poland

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Koszalin, 75-581, Poland

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Poznan, 60-569, Poland

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Siedlce, 08-110, Poland

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Tomaszów Mazowiecki, 97-200, Poland

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Warsaw, 02-781, Poland

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Lisbon, 1099-023, Portugal

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Lisbon, 1400-048, Portugal

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Lisbon, 1769-001, Portugal

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Lisbon, 1998-018, Portugal

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Loures, 2674-514, Portugal

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Porto, 4200-319, Portugal

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Changwon-si, 51353, South Korea

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Cheongju-si, 28644, South Korea

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Seongnam-si, 13620, South Korea

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Seoul, 03080, South Korea

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Seoul, 03722, South Korea

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Seoul, 05505, South Korea

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Suwon, 16247, South Korea

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Suwon, 16499, South Korea

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Barcelona, 8003, Spain

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Barcelona, 8035, Spain

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Granada, 18016, Spain

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Madrid, 28034, Spain

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Madrid, 28040, Spain

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Santiago de Compostela, 15706, Spain

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Valencia, 46010, Spain

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Hsinchu, 300, Taiwan

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New Taipei City, 23561, Taiwan

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Taichung, 402, Taiwan

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Taichung, 40705, Taiwan

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Taipei, 11490, Taiwan

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Taipei, Taiwan

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Taoyuan, 333, Taiwan

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Bangkok, 10300, Thailand

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Bangkok, 10700, Thailand

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Hat Yai, 90110, Thailand

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Khon Kaen, 40000, Thailand

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Khon Kaen, 40002, Thailand

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Lampang, 52000, Thailand

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Muang, 22000, Thailand

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Muang, 50200, Thailand

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Mueang, 20000, Thailand

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Naimuang, 30000, Thailand

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Ankara, 06010, Turkey (Türkiye)

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Ankara, 06230, Turkey (Türkiye)

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Ankara, 06800, Turkey (Türkiye)

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Cordaleo, 35575, Turkey (Türkiye)

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Diyarbakır, 21280, Turkey (Türkiye)

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Goztepe Istanbul, Turkey (Türkiye)

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Belfast, BT9 7AB, United Kingdom

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Bristol, BS2 8ED, United Kingdom

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Dundee, DD1 9SY, United Kingdom

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Edinburgh, EH4 2XR, United Kingdom

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London, NW1 2PG, United Kingdom

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London, W6 8RF, United Kingdom

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Middlesbrough, TS4 3BW, United Kingdom

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Poole, BH15 2JB, United Kingdom

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Torquay, TQ2 7AA, United Kingdom

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Truro, TR1 3LJ, United Kingdom

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Wolverhampton, WV10 OQP, United Kingdom

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Haiphong, 180000, Vietnam

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Hanoi, 100000, Vietnam

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Ho Chi Minh City, 700000, Vietnam

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Related Publications (1)

  • Barlesi F, Cho BC, Goldberg SB, Yoh K, Zimmer Gelatti AC, Mann H, Gopinathan A, Bielecka ZF, Newton M, Aggarwal C. PACIFIC-9: Phase III trial of durvalumab + oleclumab or monalizumab in unresectable stage III non-small-cell lung cancer. Future Oncol. 2024;20(29):2137-2147. doi: 10.1080/14796694.2024.2354160. Epub 2024 Jul 18.

Related Links

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

durvalumabmonalizumab

Condition Hierarchy (Ancestors)

Carcinoma, BronchogenicBronchial NeoplasmsLung NeoplasmsRespiratory Tract NeoplasmsThoracic NeoplasmsNeoplasms by SiteNeoplasmsLung DiseasesRespiratory Tract Diseases

Study Officials

  • Fabrice Barlesi, MD

    Gustave Roussy, Cancer Campus, Grand Paris

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Masking Details
Double-Blind
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 14, 2022

First Posted

February 3, 2022

Study Start

February 7, 2022

Primary Completion (Estimated)

June 30, 2026

Study Completion (Estimated)

July 2, 2030

Last Updated

January 27, 2026

Record last verified: 2026-01

Data Sharing

IPD Sharing
Will share

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

Shared Documents
STUDY PROTOCOL, SAP
Time Frame
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Access Criteria
When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
More information

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